When the Vanderbilt Amyloid Multidisciplinary Program (VAMP) launched in 2011, it was the first center in Tennessee dedicated to patients with amyloidosis – a rare, systemic disorder that encompasses myriad presentations and organ dysfunctions.
Since then, VAMP has paved the way to coordinated care as a major referral center in the southeastern United States, growing to include over a dozen collaborating specialists working to provide structured, multidisciplinary care to adults navigating an amyloidosis diagnosis.
Diagnosis of the condition requires exceptional rigor, and treatment plans readily cross specialties, says Muhamed Baljevic, M.D., VAMP director and an associate professor of hematology and oncology at Vanderbilt University Medical Center.
“VAMP was established with the aim to standardize and streamline expert clinical management of amyloidosis patients,” Baljevic said. “We do this through accurate and timely diagnosis, access to leading standards of care as well as promising research treatments, and subsequent close disease monitoring.”
Managing Complex Condition
Amyloidosis occurs when misfolded amyloid protein accumulates in extracellular tissues. There can be renal, hepatic, cardiac, gastrointestinal, or peripheral nerve involvement, among other presentations. For some patients, it may be inherited or associated with blood cancers.
Patients typically see multiple subspecialists for the extensive workup that can include blood work, urinalyses, imaging and biopsy.
Through their work, the Vanderbilt team is highlighting standardized diagnostic criteria for different types of amyloidosis, and is looking to new frontiers for improved outcomes.
“VAMP has steadily grown over the past 12 years and has welcomed multiple new faculty members in hematology-oncology, cardiology and nephrology,” Baljevic said, adding that as their footprint has grown, the number of patient referrals has followed suit.
Front-line Therapies
Amyloidosis is a highly heterogenous condition, with amyloid deposits representing one of more than 40 different protein precursors of amyloid fibrils known to cause disease, Baljevic says. Understanding the underlying protein is key to inform treatment.
Vanderbilt has been a study site for several clinical trials investigating treatment options for common, treatable forms of amyloidosis, such as systemic light chain and transthyretin amyloidosis, and for certain forms of familial amyloid cardiomyopathy.
“For transthyretin amyloidosis, as one example, Vanderbilt has participated in the ATTR-ACT and APOLLO-B trials, and we have completed enrollment for CARDIO-TTRansform. We have also participated in THAOS, which developed a multicenter international registry for transthyretin amyloidosis,” said Rebecca Hung, M.D., Ph.D., an assistant professor of cardiovascular medicine at Vanderbilt.
The Vanderbilt team is also planning to participate in trials that will further test the recombinant antibody NI006 designed to remove cardiac amyloid deposits, Hung added.
Multiple Options
For such a systemic condition, patients often benefit from concomitant therapies available at VAMP, said Salyka Sengsayadeth, M.D., an associate professor of hematology and oncology at Vanderbilt. Several novel agents tested at Vanderbilt and are now widely available.
“We are particularly excited to have contributed in the development of anti-fibril monoclonal antibody agents in light chain amyloidosis, which are being given in conjunction with plasma cell-targeting standard of care therapy,” Sengsayadeth said.
Sengsayadeth is currently the principal investigator of two phase 3 clinical trials evaluating the efficacy of one of these monoclonal antibody agents (CAEL-101) in patients with cardiac involvement, in hopes of evaluating whether the addition of these novel medications can improve patient outcomes.
“This is of particular value, as a significant portion of patients present with some form of organ compromise from amyloid deposits, and dual targeting of this type hopes to achieve better organ response metrics than what we have been able to achieve with the current standards,” Baljevic added.
Other ongoing work by the Vanderbilt team includes research into amyloidosis etiology, including identification of potential biomarkers of disease states, and development of advanced non-invasive diagnostic tools to support disease monitoring, Baljevic said.
